There is a growing need for a home diagnostic system for monitoring various personal physical health conditions and for the early detection of health problems. Such systems are typically used to determine fertility periods, pregnancy, labor onset, alcohol levels, glucose levels of diabetic persons and indicators that signal a need for comprehensive HIV testing. Home diagnostics systems are desirable because they are convenient to use and reduce health care costs.
(1) Field of the Invention
The present invention relates to saliva-monitoring oral devices including saliva-monitoring electrical toothbrushes.
(2) Related Art
Several patents describe various systems for collecting and diagnosing the contents of saliva. Some of the prior art diagnostic purposes and collection and testing procedures are summarized below.
U.S. Pat. No. 3,968,011 by Manautou et al. shows the use of optical density curves of saliva samples to indicate pregnancy. Such curves have a first peak and a smaller second peak in daily measurements; however, the second peak is eliminated when pregnancy occurs. In application, a paper test strip impregnated with a peroxidase and guaiac shows a color change when wet with saliva during the fertile period. The change is caused by the presence of peroxide in the saliva. The test strip is costly and may not be reused. U.S. Pat. No. 4,385,125 by Preti et al. monitors saliva for the concentration of certain long-chain alcohols, particularly dodecanol, for detecting ovulation. The dodecanol content of saliva remains at a relatively constant level throughout the menstrual cycle, but exhibits a single peak at the time of ovulation. Because the method is complicated, it is more suitable for laboratory tests than home use. Several commercially available hand held devices predict ovulation based on a measured peak in electrical resistance corresponding to sodium and potassium electrolyte levels which are reflective of hormone changes that occur several days before ovulation. The measured data on the changes of electrolytes in saliva may be inconsistent since an oral sensor probe is placed on the tongue where the thickness of the saliva layer may vary. While there are disadvantages associated with all of the above methods, each method demonstrates the feasibility of using an optical sensor or a conductivity sensor for measuring signals derived from a saliva sample to predict an ovulation period or pregnancy.
U.S. Pat. No. 5,480,776 by Dullien discloses a method for detecting the onset of labor by analyzing a body fluid, such as saliva, for estriol hormone concentration. The method correlates the estriol concentration with a standard value and relates the rate of increase of the concentration as an indicator of the onset of labor. A preferred assay utilizes an enzyme-labeled component in a competitive binding assay for estriol. In a typical assay, antibody is attached to a solid surface such as a porous reagent strip. The antibody-coated solid surface is then contacted simultaneously with a sample and with a competitive binding compound. After reaction, if sufficient estriol is present in the sample, then no enzyme is present to produce a color change (positive result). Otherwise, a change of color indicates the absence of estriol in the sample (negative result). This method is most effective when the rate of increase of estriol hormone is monitored on a daily or regular basis.
Saliva may also be used to test blood alcohol level. Ethyl alcohol is a component of the blood that perfuses the salivary glands. The ethanol content of saliva has been determined through measurements to be about 9% higher than capillary blood alcohol content. However, U.S. Pat. No. 5,968,746 to Schneider et al. indicates a high correlation coefficient (r=97) between ethanol concentrations in simultaneously drawn blood and saliva samples. The test unit described in the patent uses a vacuum-packed ampoule containing dried enzyme, a solution swellable plug and a suitable colorimetric reagent. Since the test is activated by breaking the ampoule, it is not re-useable and the test is not suitable for home use. The test strip method of U.S. Pat. No. 4,786,596 to Adams, uses alcohol oxidase, peroxidase and a hydrogen donor indicator such as tetraalkalbengidine in a carrier matrix supported on the strip. The alcohol oxidase functions as a catalyst to convert any ethanol present along with ambient oxygen to acetaldehyde and hydrogen peroxide. The peroxidase functions as a catalyst to induce a color change in the hydrogen donor indicator and converts the hydrogen peroxide to water. Because this method requires the use of a color chart to visually identify the alcohol concentration, it is subject to interpretation errors. The test procedure does, however, confirm the effectiveness of testing alcohol concentration by using saliva.
Efforts have been made to develop a noninvasive monitoring procedure for blood glucose using a saliva sample instead of drawing a test blood sample from a finger. U.S. Pat. No. 6,102,872 by Doneen et al. discloses that glucose concentration of oral fluid is approximately 0.5% to 1.0% of the contemporaneous blood concentration. The patent details the correlation between measured oral glucose level and the concentration of blood glucose. The patentee uses a small pore size membrane having sodium citrate mixed with citric acid for stimulating saliva secretion and collecting filtered saliva. The filtered saliva is in contact with a colorimetric glucose film. The film contains the enzymes glucose oxidase and horseradish peroxidase, and a combination of dyes and accessory reagents, such as buffers and stabilizers, for producing a colored spot or line with color intensity proportional to the glucose concentration in the saliva sample. In application, reflectance measurements by a spectrophotometer are converted into an estimated blood glucose value with the use of a computational chip in a monitor.
U.S. Pat. No. 5,500,374 by Wenzhi uses a UV detector and electrostatic ion chromatography to produce a chromatogram from a saliva sample. Diagnosis for diabetes mellitus is based on the presence or absence of a chromato-peak of the diabetes mellitus-specific component. Since the saliva sample is required to be injected into a stationary phase in a separation column, the method is not suitable for home use. In U.S. Pat. No. 4,105,522 to Friedenberg et al., the concentration level of glucose in saliva is determined by oxidizing a test sample with an oxidizing agent and measuring the electrical potential (in millivolts) of a primary cell in which the residual oxidizing solution is the electrolyte. U.S. Pat. No. 5,264,103 by Hoshioka, U.S. Pat. No. 5,997,817 by Crismore et al. and U.S. Pat. No. 6,004,441 by Fuziwara et al. use a dry reagent layer of specific chemical compositions and a biosensor of a special electrode arrangement for testing glucose concentration. The dry reagent layer is dissolved in a blood sample. The biosensor is not renewable, i.e. it can not be regenerated for subsequent use.
Saliva is also used to test for HIV indicators. Advantages of using saliva samples instead of blood test samples are avoidance of costly handling and reduction in health risks to workers. While HIV is not known to be transmitted in saliva, it is present in saliva. A published research article, xe2x80x9cThe Diagnostic Uses of Saliva,xe2x80x9d J. Oral Pathol. and Medicine, 19:119-125 (1990), suggests that saliva be used as a source for screening for anti-HIV antibodies. Furthermore, a commercial anti-HIV assay kit has been developed for the purpose of detecting anti-HIV antibodies in saliva. In U.S. Pat. No. 5,695,930 by Weinstein et al., a HIV test kit method for detecting anti-HIV-I antibodies in saliva is described. To enable confidentiality and convenience of frequent testing, the patent discloses an inexpensive assay kit for anti-HIV antibodies in saliva that can be personally performed at home without the need for a laboratory immunoassay. It uses an enzyme reporter molecule of alkaline phosphatase that promotes a reaction which is detected by a change in color of the reactants. The patent also describes a solid phase immunoassay for testing in three steps. The first step uses a test strip having nitrocellulose-bound proteins in direct contact with saliva for 30 minutes; the second and third steps involve incubating the test strip with goat anti-human IgG and with a NBT/X phos substrate, respectively. Test results show either a blue spot which indicates a positive test for anti-HIV antibodies in the saliva, or a white spot which indicates a negative test. Although this method involves repeated washing and incubation of a test strip, the feasibility of using saliva to test for HIV is promising for use in home diagnostic systems if test procedures are simplified and economized.
The foregoing patents demonstrate various procedures and equipment used for testing saliva for ovulation, pregnancy, labor onset, alcohol, glucose concentration, and HIV.
The prior art has disclosed various means for collecting saliva samples. U.S. Pat. No. 4,834,110 by Richard describes a suction cup for collecting a saliva sample. Suction is applied to a person""s cheek around the parotid salivary duct and a pulsing pressure or electrical stimulation is applied to promote the flow of saliva to a collector vessel. This method requires the soft rim of the cup to be in full contact with the cheek and with a partial vacuum pressure for suction. The device is for one-time use in laboratory testing. Another device that uses a collecting cup for monitoring saliva is disclosed in U.S. Pat. No. 6,061,586 by Kuperman et al. The device includes a sample kit and an electrode assembly for immersion within a patient""s saliva. The sample kit is comprised of a syringe-like element with a piston and a sponge member for absorbing the saliva to be compressed by the piston into the collecting cup. The voltage signal is processed by a microprocessor according to a selected mathematical model. The disadvantages associated with using the kit are potential contamination of saliva by the sponge and the per use costs of the non-reusable disposable components. An in-situ testing procedure with direct contact between a non-saliva test fluid and sensors without utilization of a third medium for transporting or extraction is disclosed in U.S. Pat. No. 6,080,118 by Blythe. The insertable portion of a vaginal probe includes a number of fluid flow grooves and the probe is rotatable for stimulating the secretion of vaginal fluids for collection. The sensors are electronically coupled to integrated circuitry for analyzing measured data and are mounted on the surface of the vaginal probe to test a non-controlled quantity of test fluid between the sensors and the vaginal wall. The inconsistency of the volume of the test fluid can lead to significant measurement errors.
U.S. Pat. No. 5,684,296 by Hamblin describes a fiber optic liquid sensing system. The system uses a reflective-type optical sensor which has a housing with a highly polished reflector. The reflector is positioned at a distance opposed to the terminal surfaces of light emitting and a light receiving strands, which are bundled in side-by-side fashion. There are a number of apertures on the circumferential wall of the housing for drawing in a fluid sample for optical measurements. Although the sensor housing is compact and contains all the sensor components, the configuration of the apertures may entrap air inside the housing that causes measurement errors. Because the segmented walls between the apertures hinder thorough cleaning, the sensor is non-reusable.
U.S. Pat. No. 5,206,711 by Bethold et al uses an open channel in conjunction with a fluid opacity sensor for measuring opacity of a fluid sample in a process line. To compensate for light source drift caused by temperature effect and 60 Hz line noise in the processing electronics, a reference optical pathway having the same optical system is used and a signal processing means is provided to cancel the effects of the light source drift. The width of the channel used is designed for the passage of fluid rather than for inducing a capillary effect to draw in and hold a fixed volume of sample fluid for testing. U.S. Pat. No. 6,099,484 by Douglas et al. discloses a capillary tube for drawing body fluid from an incision and a test strip affixed to an upper end of the capillary tube for receiving the fluid. By pressing the device against the skin at the site of an incision, the test strip directly contacts body fluid emanating from the incision. To ensure that a sufficient sample size enters the tube, a drop-detecting mechanism uses either electrodes or an optical system for detecting the height of the sample drop. Similarly, U.S. Pat. No. 5,100,620 by Brenneman uses a capillary tube in conjunction with an exposed reagent pad to contact a test fluid. A vent passageway having a smaller diameter than the capillary tube is also used. Optical measurement begins as the optics system senses the start of a change in color of the reagent pad. Since both methods employ a capillary tube of small diameter (ranging from 0.01 to 0.03 inches), the fluid inside the tube cannot be washed out to clean it for repeated uses.
U.S. Pat. No. 5,851,838 by Vetter et al uses a planar capillary gap for transporting a sample fluid over the top of a diagnostic test carrier. To avoid false test results caused by continuous re-diffusion of analyte out of a test area while the test reaction is in progress, the patentee uses excess sample liquid to surround the test carrier. Since the capillary gap is not closed during testing, the test is subject to measurement errors. Although each of these patents demonstrates use of a capillary tube for transporting a fluid sample over a test strip for testing, the capillary channels and test strips are manually replaced for each use. This is inconvenient and costly for use in a home diagnostic device.
Sensors suitable for use in conjunction with small spaces such as capillary test channels, are known. U.S. Pat. No. 5,335,305 by Kosa discloses fabrication methods for installing fiber optical sensors in fiber bundles fabricated from fibers that are bent with small radii. U.S. Pat. No. 5,851,838 by Vetter et al., U.S. Pat. No. 5,997,817 by Crismore et al., and U.S. Pat. No. 6,058,934 by Sullivan show various electrode matrices arranged in planar configurations. Sullivan details the use of four terminals in which voltage measuring electrodes are separated from current carrying electrodes, enabling only a low current to be drawn from a sample. The arrangement confines the measured current to the sensor chamber, thereby preventing the conductivity sensor from interfering with other sensors in the test instrument. The patentee describes the advantage of using a planar configuration to simplify the manufacturing process and enhance efficient fluidics so that the cells can be filled and washed out with a minimal volume of reagent. The size of the chip may be, for example, approximately 0.12 by 0.12 inches and can be disposed in a flow cell receptacle in a sensor housing to form one wall of a fluid flow path on which fluid flows perpendicular to the parallel arrangement of the electrodes. The width and spacing of the electrodes are not critical, each typically being 0.005 inches. The Crismore et al patent discloses the use of palladium as the electrode surface because of its resistance to oxidization and its relatively low cost. The preferable distance between electrodes is about 1.2 mm and the exposed area of an electrode need not be entirely covered with a test reagent.
Electrodes can also be used to measure pH. U.S. Pat. No. 5,573,798 by Kato relates to a pH-measuring electrode having a sensor film of metal oxide which is sensitive to a hydrogen ion in solution. In operation, the pH-measuring electrode is immersed in the solution to be measured together with a reference electrode such as a calomel electrode or a silver-silver chloride electrode. Based on the potential difference between the two electrodes, a pH value is determined.
The combined use of an electrode matrix with a dry reagent layer for testing physiological fluids has been the subject of several patents on biosensors including U.S. Pat. No. 5,120,420 by Nankai et al., U.S. Pat. No. 5,264,103 by Yoshioka et al. and U.S. Pat. No. 6,004,441 by Fugiwara et al. Using blood drops as test samples for detecting glucose, the biosensors disclosed in these patents utilize an electrode matrix produced by screen-printing and a dry reagent layer containing an enzyme which reacts only to glucose in the blood sample. The enzyme contained in the reagent layer is dissolved in the sample liquid. According to the description contained in U.S. Pat. No. 6,004,441 by Fugiwarra et al, the electrode system of a biosensor is comprised of an electrode for measurement and a counter-electrode which functions as a reference electrode. The covering on top of the electrode matrix is a reagent layer which includes glucose oxidase as an enzyme and potassium ferricyanide as a mediator. When a voltage is applied between the electrodes, electric current flows in proportion to the concentration of glucose. Typical dimensions of an electrode matrix are 5 to 10 nm in electrode thickness and about 70 .mu.m between electrodes. For better performance, the width of each of the two counter-electrodes is preferably the same or larger than that of the measuring electrode. In operation, a drop of blood is placed on the reagent layer after the electrode system is energized. After the change in conductivity stabilizes, the voltage applied is suspended for a period of time to allow for the oxidation of glucose and the reduction of potassium ferricyanide to take place. After completion of the reaction, a voltage is applied again to cause oxidation of the reduced potassium ferricyanide. This results in an electric current which is proportional to the concentration of glucose, a measurement of the blood sugar level. The reagent layer is not reusable.
U.S. Pat. No. 5,208,147 by Kagenow et al. discloses a method for using a discardable measuring device and a conditioning fluid chamber for repeated release of fresh conditioning fluid for calibrating a sensor for measurements. However, the device requires the inconvenient step of moving the sensor to a conditioning fluid chamber to expose the sensor surface to the conditioning fluid.
In summary, there have been a significant number of patents which utilize saliva samples to test for fertility periods, pregnancy, labor onset, alcohol concentration, glucose concentration and HIV indicators. While various articles such as xe2x80x9cWhat""s Next: Medicinexe2x80x9d (Popular Science, July 2000, pp 50-54) discuss the need for home diagnostic devices, none is capable of performing the stimulation and collection of saliva and testing the saliva sample in an all-in-one handheld device for economic, efficient and convenient repeated regular uses at home.
It is therefore an object of this invention to provide a portable handheld diagnostic oral device which stimulates saliva production and collects saliva samples in a test channel. It is another object of the invention to test saliva samples for the purpose of monitoring selected biophysical conditions of a user on a daily basis. It is a further object of the invention to provide a portable hand held diagnostic device which has a toothbrush component.
These and other objects of the invention are accomplished with a saliva-monitoring oral device which is inserted into the mouth to collect and test saliva. As an all-in-one, handheld diagnostic device, it stimulates saliva production and collects it in a test channel where measurements are conducted by sensors. Measured data is stored and analyzed for abnormalities by a microprocessor included in the handle of the device. During testing, various kinds of reagents may be used depending on the type of test (fertility, pregnancy, labor onset, alcohol content, glucose concentration, HIV indicators, etc.) being conducted. Each reagent is stored in a replaceable cartridge which is inserted into the handle for use in a particular test.
The preferred embodiment of the oral device is configured as a saliva-monitoring, biosensor electrical toothbrush which has a handle and a brush head. The handle contains a battery, microprocessor, motor, a rotatable and slideable driveshaft and a reservoir for storing reagent used in testing saliva. A plurality of bristles which rotate or oscillate are attached to the top of the brush head and a notch-like open channel traverses the width of the bottom of the brush head. Sensors are mounted on the walls of the test channel and a small vent groove is positioned at the bottom of the channel. A conduit with one-way check valves connects the reagent reservoir to an inlet opening in a wall of the test channel. The channel has a cover to seal it closed while testing is in progress. A display unit for the microprocessor is attached to the handle.
In operation, a switch is turned on to start the oscillation of the bristle elements. This also causes vibration of the brush head and the open test channel. When placed in contact with the tongue or cheek, the vibrating channel walls stimulate the secretion and accumulation of saliva under the tongue or elsewhere in the mouth. Saliva is drawn into the open channel by its capillary action, facilitated by a partial vacuum caused by the vibration of the channel walls. The complete filling of the open channel is detected by a sensor which is positioned at the inner most location of the open channel. At the moment of complete filling, the control system activates a solenoid which causes its actuator disk to press on an internal elastic pump button which dispenses a controlled amount of reagent into the test channel. Simultaneously, the solenoid""s actuator rod pushes the slideable drive shaft forward which causes a channel cover that is mechanically linked to the drive shaft, to close the open channel. The synchronization of the reagent dispensing and the channel closing is timed to keep the dispensed reagent inside the test channel. During these actions, the continued vibration of the channel accelerates the mixing of the reagent with the saliva sample. After a predetermined mixing time period, the sensors take readings on the optical density and/or the electrical current level which reflect the concentrations of targeted analytes of the saliva sample. The microprocessor inside the toothbrush handle compares newly measured data against established trend and threshold values to signal abnormality. The display unit is capable of providing trend data and sending acoustical or visual warning signals. The saliva collection and testing steps are usually completed within 30 seconds. After the display of the test results, the control system deactivates the solenoid to retract the actuator rod which brings the channel cover to the open or home position. After the test channel is cleansed, the toothbrush is ready to be used for brushing in the normal manner.